(1) Field of the Invention
This invention relates to a method for producing .alpha.-(p-isobutylphenyl)propionic acid. More particularly, the invention relates to a method for producing .alpha.-(p-isobutylphenyl)propionic acid by oxidizing .alpha.-(p-isobutylphenyl)propionaldehyde with a hypohalogenite at temperatures not higher than -12.degree. C. in the presence of an inorganic acid.
(2) Description of the Prior Art
The .alpha.-(p-isobutylphenyl)propionic acid (IPA) prepared according to the method of the present invention is known as a useful medicine for the relief of pain, fever and inflammation with little adverse reaction.
There are proposed many kinds of methods for producing IPA by oxidizing .alpha.-(p-isobutylphenyl)-propionaldehyde (IPN) with various oxidizing agents. For example, silver compounds are used as oxidizing agents in the methods disclosed in U.S. Pat. No. 3,965,161, French Patent No. 1,545,270, and Japanese Laid-Open Patent Publication No. 58-35140; permanganates are used in the methods disclosed in Japanese Laid-Open Patent Publication Nos. 51-100042, 51-101949 and 52-97930; and oxidizing agents such as chromic acid, peracids, hydrogen peroxide and chlorites are used in the method disclosed in British Patent Nos. 1,549,140 and 2,004,543 and Japanese Laid-Open Patent Publication No. 51-10042. These methods are, however, not satisfactory in view of industrial working, because the selectivity relative to the intended IPA is low or expensive substances must be used as oxidizing agents.
Japanese Laid-Open Patent Publication No. 53-18534 also discloses an oxidizing method, in which the hypohalogenite is used as the oxidizing agent in the presence of acetic acid. This method has, however, critical drawbacks owing to the acetic acid, details of which are mentioned later on.
The inventors of this application have carried out extensive studies on the oxidation using the salts of hypohalogenous acids.
As a result, the following facts were found out when only hypohalogenite as an oxidizing agent for IPN is employed. That is,
(1) The by-production of halides of IPA (IPA halides) as trace impurities cannot be avoided.
(2) As the main by-product is p-isobutyl acetophenone (BAP), the ratio of IPA/BAP must be improved.
(3) It is necessary to select co-existing acids with which the aimed product of IPA can be recovered efficiently.
Therefore, the selection of a more efficient method is an important factor.
Incidentally, the substance prepared by the method of the present invention is a medicine used for the relief of fever and pain. Accordingly, it is an important matter to avoid by-production of halogenated impurities, even when the quantities of them are very small. What is worse, the chemical structure of this IPA halide is close to that of IPA.
With the above consideration, the inventors of the present application found out the following important facts and accomplished the method for efficiently producing highly pure IPA.
(1) To improve the ratio of IPA/BAP.
(2) To decrease the quantity of by-produced IPA halide.
(3) To use an inorganic acid as a co-existing acid in order to recover efficiently the aimed product.